Transfer RNA-Derived Fragments, the Underappreciated Regulatory Small RNAs in Microbial Pathogenesis.

Zhongyou Li,Bruce A. Stanton

doi:10.3389/fmicb.2021.687632

Abstract

In eukaryotic organisms, transfer RNA (tRNA)-derived fragments have diverse biological functions. Considering the conserved sequences of tRNAs, it is not surprising that endogenous tRNA fragments in bacteria also play important regulatory roles. Recent studies have shown that microbes secrete extracellular vesicles (EVs) containing tRNA fragments and that the EVs deliver tRNA fragments to eukaryotic hosts where they regulate gene expression. Here, we review the literature describing microbial tRNA fragment biogenesis and how the fragments secreted in microbial EVs suppress the host immune response, thereby facilitating chronic infection. Also, we discuss knowledge gaps and research challenges for understanding the pathogenic roles of microbial tRNA fragments in regulating the host response to infection.

Highlights

To thrive in harsh conditions, micro-organisms must respond to changes in the environment, including iron deprivation, nutrient starvation, and host immune responses
In a study sequencing small RNAs (sRNAs) in Pseudomonas aeruginosa (Koeppen et al, 2016), we found that transfer RNA (tRNA) fragments are more abundant than canonical non-coding sRNAs (ncRNAs) (Figure 1D), and those tRNA fragments are differentially packaged in outer membrane vesicles (OMVs) (Figure 1E)
We demonstrated that sRNA52320, a 24-nt long 5' tRNAfMet fragment, is secreted by P. aeruginosa in OMVs that fuse with primary human primary bronchial epithelial (HBE) cells and attenuates OMV-induced IL-8 secretion and recruitment of neutrophils into mouse lung by reducing the expression of mitogen-activated protein kinases (MAPK; Koeppen et al, 2016)

Summary

Introduction

To thrive in harsh conditions, micro-organisms must respond to changes in the environment, including iron deprivation, nutrient starvation, and host immune responses. We review papers that report the role of microbial tRNA fragments secreted in extracellular vesicles (EVs) and how they regulate gene expression in the host. Microbial EVs containing sRNAs and tRNA fragments deliver their contents to recipient cells, and a few studies have shown by transfecting synthetic RNA oligos and making sRNA-deletion mutants, that sRNAs and tRNAs regulate gene expression in eukaryotic host cells (Garcia-Silva et al, 2014a; Koeppen et al, 2016; Choi et al, 2017; Zhang et al, 2020).

Results

Conclusion